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Daniel
M. Sullivan, M.D. Program Leader, Experimental Therapeutics Member-in-Residence of the H. Lee Moffitt Cancer Center E-mail:
Dan.Sullivan@moffitt.org |
Training
B.A.: University of Louisville (Biology), 1974.
M.D.: University of Louisville School of Medicine, 1981.
M.S.: University of Louisville (Biochemistry), 1982.
Fellowship in Hematology/Oncology: Department of Medicine, University
of Florida; Gainesville, FL, 1985-1988.
Internship and Residency in Internal Medicine: Department of Medicine;
University of Florida, Gainesville, FL, 1982-1985.
Research
Interests
My lab is involved in trying to determine how cancer cells become resistant
to the antitumor drugs that are to treat human malignancies. Specifically,
we are focused on defining the mechanisms of drug resistance to two classes
of antitumor agents; drugs that work by inhibiting the activity of either
DNA topoisomerase I or topoisomerase II. Topoisomerases are ubiquitous
enzymes and are necessary for normal cell function. Their activity results
in DNA single- and double-strand breaks, and thus they relieve the torsional
strain which occurs in DNA during replication. In addition to their normal
intracellular roles, topoisomerases are also the targets of several commonly
used antitumor agents-drugs used in the treatment of multiple myeloma,
leukemia, breast cancer, lung cancer, ovarian cancer and lymphomas. One
mechanism of drug resistance, which we have recently defined in human
myeloma cells, is the trafficking of DNA topoisomerase II from the nucleus
to the cytoplasm. Cells become resistant to topoisomerase II inhibitors
in this case because the enzyme is no longer located where it can cause
lethal DNA damage in the presence of the drug. Defining the signals which
are responsible for nuclear export and nuclear import are important research
goals in my laboratory. If we could prevent topoisomerase II from localizing
in the cytoplasm, it might be possible to resensitize tumor cells to these
drugs. My lab is also involved in studies which involve tumor biopsies
from patients receiving topoisomerase inhibitors, to determine if what
we have learned in the laboratory is also true in human tumors. By defining
these mechanisms of drug resistance, we hope to develop approaches to
preclude or surmount this obstacle to the successful treatment of human
cancers.
Search
for publications by: 
This
search will be conducted at the US National Library of Medicine (NLM) and PubMed.
Selected
Publications
Djulbegovic, B., Hozo, I., Fields, K.K., and Sullivan, D.M. High-dose
Chemotherapy in the Adjuvant Treatment of Breast Cancer: Benefit Risk
Analysis. Cancer Control, 5, 394-405, 1998.
Weitzner, M.A., Lehninger, F., Sullivan, D.M., Fields, K.K. Borderline Personality Disorder and Bone Marrow Transplantation: Ethical Considerations and Review. Psycho-Oncology, 8, 46-54, 1999.
Turnbull, R.M., Meczes, E.L., Rogers, M.P., Lock, R.B., Sullivan, D.M., Finlay, G.J., Baguley, B.C., and Austin, C.A. Carbamate Analogues of Amsacrine Active Against Non-cycling Cells: Relative Activity Against Topoisomerases IIa and b. Cancer Chemotherapy Pharmacology, 44, 275-282, 1999.
Hochhauser, D., Valkov, N.I., Gump, J.L., Wei, I., O'Hare, C., Hartley, J.A., Fan, J., Bertino, J.R., Banerjee, D., and Sullivan, D.M. Effects of Wild-type p53 Expression on the Quantity and Activity of Topoisomerase IIa and b in Various Human Cancer Cell Lines. Journal of Cellular Biochemistry, 75, 245-257, 1999.
Dong, Q., Johnson, S.P., Colvin, O.M., Bullock, N., Kilborn, C., Runyon, G., Sullivan, D.M., Easton, J., Bigner, J., Modrich, P. and Friedman, H.S. Multiple DNA Repair Mechanisms and Alkylator Resistance in the Human Medulloblastoma Cell Line D-283 MED (4-HC). Cancer Chemotherapy, 43, 73-79, 1999.
Valkov, N.I., Gump, J.L., Engel, R., and Sullivan, D.M. Cell Density-dependent VP-16 Sensitivity of Leukemic Cells is Accompanied by the Translocation of Topoisomerase IIa from the Nucleus to the Cytoplasm. British Journal of Haematology, 108, 331-345, 2000.
Fishman, M.N., and Sullivan, D.M. Application of Resistance Reversal Agents in Hematologic Malignancies. Hematology, 5, 343-358, 2001.
Tsai, S.-C., Valkov, N., Yang, W.-M., Gump, J., Sullivan, D.M., Seto, E. Histone Deacetylase Interacts Directly with DNA Topoisomerase II. Nature Genetics, 26, 349-353, 2000 .
Fishman, M.N., and Sullivan, D.M. Application of Resistance Reversal Agents in Hematologic Malignancies. Hematology, 5, 343-358, 2001.
Hazlehurst, L.A., Valkov, N., Wisner, L., Storey, J.A., Boulware, D., Sullivan, D.M., and Dalton, W.S. Reduction in Drug-induced DNA Double Strand Breaks Associated with b 1 Integrin-mediated Adhesion Correlates with Drug Resistance in U937 cells. Blood, 15, 1897-1903, 2001.
Valkov, N.I., and Sullivan, D.M. Tumor p53 Status and Response to Topoisomerase II Inhibitors. Drug Resistance Updates, 6, 27-39, 2003.
Engel, R., Valkov, N.I., Sullivan, D.M. Drug Resistance to DNA Topoisomerase I and II Inhibitors. Recent Research Developments in Cellular Biochemistry, 1, 207-232, 2003
Engel, R., Valkov, N., Gump, J., Hazlehurst, L., Dalton, W.S., and Sullivan, D.M. The Cytoplasmic Trafficking of DNA Topoisomerase II a Correlates with Etoposide Resistance in Human Myeloma Cells. Experimental Cell Research, 295, 421-431, 2004.
Turner, J.G., Engel, R., Derderian, J.A., Jove, R., and Sullivan, D.M. Human Topoisomerase II a Nuclear Export is Mediated by Two CRM-1-dependent Nuclear Export Signals Journal of Cell Science, 117, 3061-3071, 2004.
Marchion, D.C., Bicaku, E., Daud, A.I., Richon, V., Sullivan, D.M., and Munster, P.N. Sequence-specific Potentiation of Topoisomerase II Inhibitors by the Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid. Journal of Cellular Biochemistry, 92, 223-237, 2004.
Alsina, M., Fonseca, R., Wilson, E.F., Belle, N., Gerbino, E., Price-Troska, T., Overton, R., Ahmman, G., Bruzek, L., Adjei, A., Kaufmann, S., Wright, J., Sullivan, D.M., Djulbegovic, B., Cantor, A., Greipp, P.R., Dalton, W.S., and Sebti, S.M. Farnesyltransferase Inhibitor Tipifarnib is Well Tolerated, Induces Stabilization of Disease and Inhibits Farnesylation and Oncogenic/Tumor Survival Pathways in Patients with Advanced Multiple Myeloma. Blood, 103, 3271-3277, 2004.
Yen, Y., Margolin, K., Doroshow, J., Fishman, M., Johnson, B., Clairmont, C., Sullivan, D.M., and Sznol M. A Phase I Trial of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone in Combination with Gemcitabine for Patients with Advanced Cancer. Cancer Chemotherapy and Pharmacology, 54, 331-342, 2004.
In Press
Sood, A.K., Lush, R., Geisler, J.P., Shahin, M.S., Sanders, L., Sullivan, D.M., Buller, R.E., and Sorosky, J.I. Sequential Intraperitoneal Topotecan and Oral Etoposide Chemotherapy in Recurrent Platinum-Resistant Ovarian Carcinoma: Results of a Phase II Trial. (In Press: Clinical Cancer Research, 2004).
Moulder, S.L., Mahany, J.J., Lush, R., Roca-Lima, C., Ferrante, K.J., Bartowski, L.M., Kajiji, S., Noe, D., Paillet, S., and Sullivan, D.M. A Phase I Open Label Study of CP-609,754, a Farnesyltransferase Inhibitor in Patients with Advanced Malignant Tumors. (In Press: Clinical Cancer Research, 2004).
Lush, R.M., McClure, J., Tetteh, L., Mahany, J.J., Garland, L., Learned-Coughlin, S., Suttle, B., and Sullivan, D.M. The Absolute Bioavailability of Oral Navelbine in Patients with Solid Tumors. (In Press: Cancer Chemotherapy and Pharmacology, 2004).
Submitted
Valkov, N., Turner, J., Agrawal, D., Gump, J., and Sullivan, D.M. Characterization of Myeloma Patient Bone Marrow Stromal Cell Lines with Endothelial Morphology Involved in Plasma Cell Drug Resistance. (Submitted to the American Journal of Pathology, 2004).
Daud, A., Valkov, N.V., Centeno, B., Derderian, J., Sullivan, P., Urbas, P., DeConti, R.C., Andrews, S., Berghorn, E., Hausheer, F., and Sullivan, D.M. Phase II Trial of Karenitecin (BNP 1350) in Patients with Malignant Melanoma: Clinical and Translational Study. (Submitted to Clinical Cancer Research, 2004).
Simon, G.R., Lush, R., Williams, C., Cantor, A., Antonia, S., Garrett, C., Rocha-Lima, C., Fishman, M., and Sullivan, D.M.Sequential oral 9-nitrocamptothecin and Etoposide: A Pharmacodynamic and Pharmacokinetic Based Phase I Trial. (Submitted to Clinical Cancer Research, 2004).
Fishman, M., Lush, R., Mahany, J.J., Dellaportas, A., Cantor, A., and Sullivan, D.M. Phase I Dose-escalation and Pharmacokinetic Study of Novel Taxane BMS-188797 in Combination with Carboplatin Every Three Weeks. (Submitted to Clinical Cancer Research, 2004).
Garrett, C., Rago, R., Williams, C., Dellaportas, A., Mahany, J.J., Lush, R., Dalton, W., and Sullivan, D.M. Phase I Study of a Novel Taxane BMS-188797 in Adult patients with Solid Tumors. (Submitted to Clinical Cancer Research, 2004).
Marchion, D.C., Bicaku, E., Daud, A.I., Sullivan, D.M., and Munster, P.M. Valproic Acid Alters Chromatin Structure by Regulation of Chromatin Modulation Proteins. (Submitted to Cancer Research, 2004).
Minton, S.E., Muro-Cacho, C.A., Diaz, N., Cox, C., Gritsko, T., Garcia, R., Lacevic, M., Romero, S., Tran, J., Cantor, A., Lee, J.H., Beam, C.A., Sullivan, D., and Jove, R. Phase II Neoadjuvant Trial of Dose-dense Sequential Doxorubicin and Docetaxel in High-risk Breast Cancer: Stat3 as a Novel Predictor of Response to Therapy. (Submitted to Clinical Cancer Research, 2004).
Diaz, N., Minton, S., Cox, C., Bowman, T., Gritsko, T., Garcia, R., Wloch, M., Livingston, S., Seijo, E., Cantor, A., Lee, J.H., Beam, C.A., Sullivan, D., Jove, R., and Muro-Cacho, C.A. Activation of Stat3 in Primary Tumors from High-risk Breast Cancer Patients is Associated with Elevated Levels of Activated Src and Survivin Expression. (Submitted to Clinical Cancer Research, 2004).
Gritsko, T., Turkson, J., Kaneko, S., Bowman, T., Huang, M., Diaz, N., Sullivan, D., Yoder, S., Enkemann, S., Eshrich, S., Lee, J.H., Beam, C.A., Cheng, J., Minton, S., Muro-Cacho, C.A., and Jove, R. Persistent Activation of Stat3 Signaling Induces Survivin Gene Expression and Confers Resistance to Apoptosis in Human Breast Cancer Cells. (Submitted to Clinical Cancer Research, 2004).
Cancer Biology Ph.D. Program
H. Lee Moffitt Cancer Center, MRC-4 East
12902 Magnolia Drive
Tampa, Florida 33612
Phone: 813-745-6876
E-mail: CancerPHD@moffitt.org
Copyright © 2000 University of South Florida